scholarly journals Characterization of early Alzheimer's-like pathological alterations in non-human primates with aging: a pilot study

2021 ◽  
Author(s):  
Hannah Jester ◽  
Saahj Gosrani ◽  
Huiping Ding ◽  
Xueyan Zhou ◽  
Mei-Chuan Ko ◽  
...  
Keyword(s):  
Pilot Study ◽  
Late Onset ◽  
Early Stage ◽  
Mitochondrial Morphology ◽  
Functional Correlation ◽  
Pathological Alteration ◽  
Phosphatase 2A ◽  
Amp Activated Protein Kinase ◽  
Increased Activity

Sporadic or late onset Alzheimer's disease (LOAD) is a multifactorial neurodegenerative disease with aging the most known risk factor. Non-human primates (NHPs) may serve as an excellent model to study LOAD because of their close similarity to humans in many aspects including neuroanatomy and neurodevelopment. Recent studies reveal AD-like pathology in old NHPs. In this pilot study, we took advantage of brain samples from 6 Cynomolgus macaques that were divided into two groups: middle aged (average age 14.81 years) and older (average age 19.33 years). We found multiple AD-like pathological alteration in the prefrontal cortex (but not in the hippocampus) of the older NHPs including tau hyperphosphorylation, increased activity of AMP-activated protein kinase (AMPK), decreased expression of protein phosphatase 2A (PP2A), impairments in mitochondrial morphology and postsynaptic densities (PSDs) formation. These findings may provide insights into the factors contributing to the development of LOAD, particularly during the early stage transitioning from middle to old age. Future endeavors are warranted to elucidate mechanisms underlying the regional (and perhaps cellular) vulnerability with aging and the functional correlation of such pathological changes in NHPs.

scholarly journals Association between methylation of BIN1 promoter in peripheral blood and preclinical Alzheimer’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hao Hu ◽  
Lan Tan ◽  
Yan-Lin Bi ◽  
Wei Xu ◽  
Lin Tan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Peripheral Blood ◽  
Late Onset ◽  
Early Stage ◽  
Susceptibility Gene ◽  
Subjective Cognitive Decline ◽  
Preclinical Ad ◽  
T Tau ◽  
New Evidence

AbstractThe bridging integrator 1 (BIN1) gene is the second most important susceptibility gene for late-onset Alzheimer’s disease (LOAD) after apolipoprotein E (APOE) gene. To explore whether the BIN1 methylation in peripheral blood changed in the early stage of LOAD, we included 814 participants (484 cognitively normal participants [CN] and 330 participants with subjective cognitive decline [SCD]) from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) database. Then we tested associations of methylation of BIN1 promoter in peripheral blood with the susceptibility for preclinical AD or early changes of cerebrospinal fluid (CSF) AD-related biomarkers. Results showed that SCD participants with significant AD biological characteristics had lower methylation levels of BIN1 promoter, even after correcting for covariates. Hypomethylation of BIN1 promoter were associated with decreased CSF Aβ42 (p = 0.0008), as well as increased p-tau/Aβ42 (p = 0.0001) and t-tau/Aβ42 (p < 0.0001) in total participants. Subgroup analysis showed that the above associations only remained in the SCD subgroup. In addition, hypomethylation of BIN1 promoter was also accompanied by increased CSF p-tau (p = 0.0028) and t-tau (p = 0.0130) in the SCD subgroup, which was independent of CSF Aβ42. Finally, above associations were still significant after correcting single nucleotide polymorphic sites (SNPs) and interaction of APOE ɛ4 status. Our study is the first to find a robust association between hypomethylation of BIN1 promoter in peripheral blood and preclinical AD. This provides new evidence for the involvement of BIN1 in AD, and may contribute to the discovery of new therapeutic targets for AD.

scholarly journals Symptom-based early-stage differentiation between SARS-CoV-2 versus other respiratory tract infections—Upper Silesia pilot study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Justyna Mika ◽  
Joanna Tobiasz ◽  
Joanna Zyla ◽  
Anna Papiez ◽  
Małgorzata Bach ◽  
...  
Keyword(s):  
Pilot Study ◽  
Body Temperature ◽  
Respiratory Tract ◽  
Older Patients ◽  
Respiratory Tract Infections ◽  
Early Stage ◽  
Patient Groups ◽  
Project Data ◽  
Tract Infections ◽  
Infection Stage

AbstractIn the DECODE project, data were collected from 3,114 surveys filled by symptomatic patients RT-qPCR tested for SARS-CoV-2 in a single university centre in March-September 2020. The population demonstrated balanced sex and age with 759 SARS-CoV-2( +) patients. The most discriminative symptoms in SARS-CoV-2( +) patients at early infection stage were loss of taste/smell (OR = 3.33, p < 0.0001), body temperature above 38℃ (OR = 1.67, p < 0.0001), muscle aches (OR = 1.30, p = 0.0242), headache (OR = 1.27, p = 0.0405), cough (OR = 1.26, p = 0.0477). Dyspnea was more often reported among SARS-CoV-2(-) (OR = 0.55, p < 0.0001). Cough and dyspnea were 3.5 times more frequent among SARS-CoV-2(-) (OR = 0.28, p < 0.0001). Co-occurrence of cough, muscle aches, headache, loss of taste/smell (OR = 4.72, p = 0.0015) appeared significant, although co-occurrence of two symptoms only, cough and loss of smell or taste, means OR = 2.49 (p < 0.0001). Temperature > 38℃ with cough was most frequent in men (20%), while loss of taste/smell with cough in women (17%). For younger people, taste/smell impairment is sufficient to characterise infection, whereas in older patients co-occurrence of fever and cough is necessary. The presented study objectifies the single symptoms and interactions significance in COVID-19 diagnoses and demonstrates diverse symptomatology in patient groups.

scholarly journals Development and evaluation of two different lameness models in meat goats, a pilot study

2020 ◽  
Vol 4 (4) ◽  
Author(s):  
Emily J Reppert ◽  
Michael D Kleinhenz ◽  
Abbie Viscardi ◽  
Shawnee R Montgomery ◽  
Alison R Crane ◽  
...  
Keyword(s):  
Pilot Study ◽  
Plasma Cortisol ◽  
Interphalangeal Joint ◽  
Health Concern ◽  
Distal Interphalangeal Joint ◽  
Livestock Species ◽  
Meat Goats ◽  
Distal Interphalangeal ◽  
Maximum Temperatures

Abstract Lameness is a serious health concern for livestock species. Understanding individual animal response to pain and characterization of lameness are critical when developing appropriate treatments. The objectives of this pilot study was to evaluate two different lameness models and measures for determining response to induced lameness in meat goats. Lameness was induced by intraarticular injection into the left hind lateral claw distal interphalangeal joint with either amphotericin B (Amp-B) or kaolin-carrageenan (K-C). Response to lameness was characterized by behavior scoring, visual lameness scoring (VLS), infrared thermography (IRT) of the affected digit, pressure mat gait analysis (PMT), and plasma cortisol (CORT) analysis. Lame goats had higher VLS compared to controls (P = 0.003). Maximum temperatures measured in hooves from lame vs control goats were significantly higher (P = 0.003). Pressure mat analysis demonstrated, when compared to controls, lame goats had decreased force (P = 0.013), impulse (P = 0.007), contact pressure (P = 0.007), and contact area of the left hind limb (P = 0.009). Mean CORT levels 4 and 6 h after lameness induction were higher in lame goats (P = 0.005, P = 0.01). The two lameness methods reliably induced lameness of varying severity in healthy meat goats.

scholarly journals Correction to: Eye-tracking-aided characterization of saccades and antisaccades in SYNE1 ataxia patients: a pilot study

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Laszlo Szpisjak ◽  
Gabor Szaraz ◽  
Andras Salamon ◽  
Viola L. Nemeth ◽  
Noemi Szepfalusi ◽  
...  
Keyword(s):  
Pilot Study ◽  
Eye Tracking

An amendment to this paper has been published and can be accessed via the original article.

Exploring wall shear stress spatiotemporal heterogeneity in coronary arteries combining correlation-based analysis and complex networks with computational hemodynamics

2020 ◽  
Vol 234 (11) ◽  
pp. 1209-1222 ◽  
Author(s):  
Karol Calò ◽  
Giuseppe De Nisco ◽  
Diego Gallo ◽  
Claudio Chiastra ◽  
Ayla Hoogendoorn ◽  
...  
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Complex Networks ◽  
Coronary Arteries ◽  
Early Stage ◽  
Flow Direction ◽  
Computational Hemodynamics ◽  
Time Histories ◽  
Wall Shear

Atherosclerosis at the early stage in coronary arteries has been associated with low cycle-average wall shear stress magnitude. However, parallel to the identification of an established active role for low wall shear stress in the onset/progression of the atherosclerotic disease, a weak association between lesions localization and low/oscillatory wall shear stress has been observed. In the attempt to fully identify the wall shear stress phenotype triggering early atherosclerosis in coronary arteries, this exploratory study aims at enriching the characterization of wall shear stress emerging features combining correlation-based analysis and complex networks theory with computational hemodynamics. The final goal is the characterization of the spatiotemporal and topological heterogeneity of wall shear stress waveforms along the cardiac cycle. In detail, here time-histories of wall shear stress magnitude and wall shear stress projection along the main flow direction and orthogonal to it (a measure of wall shear stress multidirectionality) are analyzed in a representative dataset of 10 left anterior descending pig coronary artery computational hemodynamics models. Among the main findings, we report that the proposed analysis quantitatively demonstrates that the model-specific inlet flow-rate shapes wall shear stress time-histories. Moreover, it emerges that a combined effect of low wall shear stress magnitude and of the shape of the wall shear stress–based descriptors time-histories could trigger atherosclerosis at its earliest stage. The findings of this work suggest for new experiments to provide a clearer determination of the wall shear stress phenotype which is at the basis of the so-called arterial hemodynamic risk hypothesis in coronary arteries.

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